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PMEPA1 inhibits TCF-β and suppresses bone metastases in prostate cancer


In this paper, Fournier et al. show that the TGF-β regulated gene prostate transmembrane protein androgen induced-1 (PMEPA1) has an essential role in the development of bone metastases in prostate cancer.

Specifically, TGF-β increases PMEPA1 transcription in cancer cells and, in turn, membrane-bound PMEPA1 inhibits TGF-β SMAD signaling. Conversely, the knockdown of PMEPA1 in prostate cancer cells increases TGF-β signaling and the development of bone metastasis in animals. This concurred with evidence from human databases. PMEPA1 expression on prostate cancer patients is lower in those with confirmed bone metastases. Men whose PMEPA1 expression was low also showed a shorter time to the development of metastases.

Since knockdown of Pmepa1 in mice reduced the growth of lung cancer cells in a separate study, it is likely that these opposing functions of PMEPA1 are dependent on the microenvironment in which metastases develop, and possibly also on the type of cancer involved.

Editor's comment: PMEPA1 could be used as a prognostic marker to indicate to clinicians which patients were more likely to develop metastases. If the activities of the membrane-bound PMEPA1 could be enhanced, this could lead to more therapeutic options to prevent bone metastasis in men deemed to be at high risk of metastasis to sites rich in TGF-β.

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